Radiological imaging includes the use of X-Rays or radiopharmaceuticals to produce an image, and/or qualitatively and/or to quantitatively determine the functionality of, for example, a specific compartment such as the bronchi in the lungs, or organ such as the lungs, or organ system such as the pulmonary encompassing the tracheal-bronchial-alveoli gas spaces, pulmonary arterio-venous system, and soft lung tissue.
Radiological imaging using X-Rays includes computerized and non-computerized imaging equipment. It is a definite trend in radiology for X-Ray based imaging technology to be computerized, allowing for software driven new imaging techniques, digital storage of files, and evaluation or manipulation of the basic stored data at some time after the original study, all of which improve the benefits that can be derived from the patient's exposure to radiation. Examples of three dimensional technologies include but are not limited to computerized tomography (CT), high speed computerized tomography, high resolution computerized tomography, and software based three dimensional reconstruction and helical, spiral and volumetric continuous scanning which allows a CT to produce a three dimensional image of for example the lungs or heart which can be viewed from any angle aspect and/or any depth. Examples of two dimensional technologies include digital radiography, digital subtraction radiography, and digital subtraction angiography. Computerized tomographic devices exist in virtually all hospitals, while the number of computerized two dimensional devices are rapidly growing. Because of its increased sensitivity to X-Rays, computerized X-Ray imaging systems can provide the advantage of a reduced dose of radiation to the patient, and/or a highly focused beam of radiation to the specific target organ of interest thereby avoiding undesirable exposure to other and possibly radiosensitive parts of the body, and/or the ability to accurately record images and data in coordination with organ motion using, for example, an electronic physiological trigger.
X-Ray based radiological imaging depends on the difference in attenuation or absorption of X-Rays by different types of tissue. Because of the high spatial resolution of two and three dimensional computerized X-Ray devices, images and data sets can rovide diagnostic information on smaller and more discrete sections of tissue. Because of the ability to obtain images and data sets at high speed unencumbered by the limitations imposed by the physics of isotope decay, two and three dimensional computerized X-Ray devices can generate more finite rate of flow and change in gas or blood distribution information and generate images with sharper edges due to less shadowing from organ/tissue movement. By itself, X-Ray radiology is used to image hard tissue such as bone, or, soft tissue, where there has been a change in structure due to disease or trauma which would change the density of the tissue. Examples of such medical applications are bone fractures, dead tissue and tumors of certain types at certain stages of their evolution. It is desirable to increase the contrast which can be attained between different types of soft tissue, an inside cavity and the soft tissue shaping that cavity, different soft tissue structures, and to evaluate the patency and condition of the arterio-venous system using X-Rays. To this end there have been developed certain contrast enhancement agents which are employed to increase the contrast and thus the quality of a radiological or X-Ray image.
Ionic and non-ionic iodine based X-Ray contrast enhancement agents are often used to better differentiate the arterio-venous system from the surrounding soft tissue and bone and to detect abnormalities in the arterio-venous system. Because iodine has a high atomic number, it absorbs or attenuates X-Rays in proportion to its presence. Iodine based contrast enhancement agents are injected intravenously and so their use involves an invasive procedure. The primary use of iodine based contrast agents is in the diagnosis of disease and appraisal of therapy concerning the arterio-venous system, which they improve the visualization of. Iodine based contrast enhancement agents stay in the vascular system unless the blood vessel is damaged by disease. They are also used to detect abnormalities within the blood vessels such as occlusions or aneurysms.
Because they are only vascular or fluid contrast agents, iodine based contrast agents cannot be used to detect and diagnose diseases in gas containing spaces such as those in the pulmonary system, involving obstructions of the tracheal-bronchial air passages, or non-functioning areas of the lungs where elasticity has been lost and gases are no longer readily exchanged during inhalation or exhalation as in emphyzema, or where the exchange of gases from the alveolar gas sacs in the lungs across the alveolar-capillary membrane into the blood and back again is not fully occuring, or if in a lung cancer patient whether ventilation is occurring in bullae which can lead to infection and other problems, or to assess what is the optimum gas mixture and pressure for respiratory therapy or ventilator support.
It is desirable to have a radiological imaging method that allows the performance of radiological imaging such as, for example pulmonary ventilation and bronchogram radiological imaging procedures by contrasting the internal gas filled compartments with the soft tissue that forms and also surrounds those gas compartments.
For this and other reasons, there has been developed a procedure using alternating breaths of stable xenon and oxygen, or the inhalation of a mixture containing a higher than atmospheric concentration of stable xenon with oxygen. The stable xenon is partially radiopaque to X-Rays due to its high atomic number and therefore attenuates or absorbs X-Rays in proportion to the concentration in areas of the body where X-Rays passed through a patient. Wherever the stable xenon is located, the absorption of X-Rays by the stable xenon makes that area appear, depending on the image recording or output device being used, either darker or lighter, or a different color, where the degree of darkness or lightness or color being a relative enhancement of the visual image and differentiation of one area from the other. The oxygen serves a life support function.
There are two major problems with the use of stable xenon in X-Ray contrast enhancement. One problem is the high cost of stable xenon. The other is that stable xenon is a relatively dense gas. At high concentrations it can potentially require greater effort by the well or ill patient for repeated respiration although not at a level placing the patient in distress or danger. This difficulty may be present to a greater degree in patients with pulmonary illnesses. Because of its density and the fact that a patient undergoing a pulmonary ventilation or bronchogram imaging procedure is in an upright position or supine position, stable xenon or a gas mixture containing a high concentration of stable xenon, tends to flow to the lowest area of the lungs due to gravity resulting in an uneven distribution of the stable xenon throughout the lungs and uneven exhalation that is not truly reflective of the patients pulmonary status, potentially negating the diagnostic value of a study. The result may be lowered contrast in upper areas of the tracheal-bronchial-alveolar gas space structures. While this may allow superior imaging of those portions of the gas spaces such as the bronchioles and alveoli that cannot be seen by other means due to the higher resolution of the computerized X-Ray systems, it could also provide an inferior or incomplete diagnostic assessment.
Accordingly, it is an object of this invention to provide an improved radiological imaging method which can provide improved contrast enhancement which may be especially suitable in computerized X-Ray radiological imaging procedures.
It is another object of this invention to provide an improved radiological imaging method wherein a contrast enhancement agent may be provided to a patient non-invasively, such as by inhalation, which can provide contrast enhancement that allows the performance of both bronchograms of the tracheal-bronchial gas space compartments extended to the smaller bronchioles, and pulmonary ventilation studies down to the level of the alveoli, using two or three dimensional computerized X-Ray imaging equipment.
The above and other objects which will become apparent to one skilled in the art upon a reading of this disclosure are attained by the present invention which is:
A method for carrying out radiological imaging of a patient comprising providing to the patient stable xenon, oxygen and helium and thereafter performing radiological imaging of the patient.
As used herein, the term "radiologic imaging" refers to either traditional X-Ray imaging where a patient is placed between an X-Ray source and a cassette containing a film screen and film, whereby the X-Rays reaching the film screen cause it to scintillate recording an image on the film, or "computerized X-Ray", imaging.
As used herein, the term "computerized X-Ray" means a process by which X-Rays are emitted by an X-Ray tube, go through a patient, are detected electronically, are stored in digital form, images are formed by software and displayed on a CRT and/or recorded in visual or digital form.
As used herein, the term "radiological contrast" or "contrast enhancement" means the property of being able to distinguish a compartment, organ, or tissue type of interest from others on a radiological image based on the degree of differentiation in the attenuation of X-Rays.
As used herein, the term "quantitative" means diagnostic information that can be expressed in numerical terms, describing the functionality or lack thereof of a specific organ or system in the body.
As used herein, the term "trachea" refers to the large gas passage outside the lungs.
As used herein, the term "bronchi" refers to the larger gas passages in the lung and "bronchiole" refers to the smaller gas passages in the lungs.
As used herein, "alveoli" refer to the gas sacs in the lung at the terminal end of the bronchioles, where gases are exchanged between the lung and the blood across what is referred to as the alveolar-capillary membrane, with oxygen entering the blood and being consumed in cellular metabolism, carbon dioxide being produced during cellular metabolism and exiting the blood back into the lung, and xenon crossing back and forth unchanged.
As used herein, the term "pulmonary ventilation" study means the evaluation of the capacity of the lungs to inhale and exhale, the distribution of gases in the lungs and the ability of the lungs to exchange gases with the blood via the alveolar-capillary membrane.
As used herein, "wash-in" refers to the inhalation of a gas mixture, during which the distribution and rate of distribution of the gas into the gas spaces/air passages is recorded.
As used herein, "equilibrium" refers to the point at which the diagnostic gas mixture which continues to be administered has fully distributed in the gas spaces to where it is going to go, or, if blood levels of the gas are being measured, the gas concentration in the blood has plateaued and approximately equals the concentration being administered.
As used herein, "washout" refers to the elimination and rate of elimination of a diagnostic gas mixture from the gas spaces and air passages after administration of the gas mixture has been ended.
As used herein, the term "bronchogram" means the evaluation of the trachea, large bronchi and smaller bronchiole gas passages in the lungs for obstructions and/or a reduction in the size of the air passages.
As used herein, the term "pulmonary angiogram" means the evaluation of the arteriovenous system in the lungs through the use of iodine based contrast enhancement using X-Ray based imaging systems.
As used herein, the term "cardiac angiogram" means the evaluation of the arteriovenous system going into and exiting the heart and including the flow of blood in the heart through the use of iodine based contrast enhancement using X-Ray based imaging systems.
As use herein, "CT" refers to a computerized three dimensional X-Ray imaging system which using an X-Ray source, detector, and specialized software, allows the accumulation, viewing and quantification of data in slices such that a specific area such as the entire chest, organ such as the lung, or compartment such as the bronchi in the lungs, may be viewed and analyzed either on a slice per slice basis, in sections combining several slices, or in its entirety using helical, spiral or volumetric continuous scanning and three dimensional reconstruction methods which allow the viewing of the target area at any level, depth or angle aspect.
As used herein, digital, radiography, digital fluoroscopy, digital subtraction fluoroscopy and digital subtraction angiography are high resolution two dimensional radiological imaging X-Ray systems which using an X-Ray source, detector, and specialized software, allow the two dimensional reconstruction of an image which can be stored in digital form, allowing for example the enlargement of a section for better diagnosis.
Subtraction capabilities allow, for example, the taking of an image without contrast enhancement of the anatomical fixed density bone and soft tissue, followed by taking an image after the administration of contrast enhancement of the target organ or compartment without moving the patient, whereby the first image can be substracted from the second, resulting in an image of the distribution of the contrast agent.
As used herein, the terms "renal blood flow" and "liver blood flow" refer to the imaging and quantification of the rate of blood flow into, within and out of the organs, to determine the patency of blood flow and organ function, whereby such information is of particular value in the determination of the need for a transplant, the selection of an organ for transplanting, and the evaluation of an organ after it is transplanted.
As used herein, the term "cerebral blood flow" refers to the flow of blood through the capillaries of the brain and across the blood brain barrier into brain cells, and which is reflective of which areas of the brain are receiving the required rate of flow to sustain the delivery of oxygen and nutrients for brain cell function, and where the visualization and quantification of cerebral blood flow is useful in evaluation of cerebrovascular diseases such as stroke, low blood flow also known as ischemia, trauma and brain death, and where xenon being soluble in blood plasma is a useful contrast enhancement agent for this purpose.
As used herein, the term "brain tissue function" refers to the relative functioning of normal and abnormal brain cells of the same type, of different types, and the determination of brain death, where the visualization of this function is useful in the evaluation of diseases such as epilepsy, ahlzeimers, and dementia, and where xenon is useful as a contrast agent because it is first soluble in blood plasma, second can cross the blood brain barrier mimicking the exchange of oxygen between the blood and brain cells, and third is soluble in lipids or fat, which is contained in different amounts by different types of brain tissue and in the same brain tissue dependent on how well those brain cells are functioning, where the degree of enhancement by stable xenon is therefore reflective of function.
As used herein, the term "non-invasive" means not requiring breaking the integrity of the body surface such as is required with an injection to administer a substance. Inhalation of a gas is considered to be a non-invasive procedure because the gas is inhaled during the normal act of breathing. Procedures that are invasive carry with them added risk of problems at the injection site and the breaking of the sterility of the arterio-venous system.